The present invention relates to a process for synthesizing O-substituted oxime compounds. In particular, the present invention relates to the synthesizing of O-substituted oxime compounds, which process is especially useful in the conversion thereof to the corresponding O-substituted hydroxylamine.
Typically, O-alkyl oximes have been produced by reacting an oxime with an organohalide, such as methyl bromide or methyl iodide, and an alkali metal alkoxide, such as sodium methoxide. For example, Dunstan and Goulding in J. Chem. Soc., 23, 628, 1901 disclose the O-methylation of acetone oxime by reacting acetone oxime with methyl iodide and sodium methoxide.
EPO Patent Application No. 23,560 to Linhart et al. discloses two procedures for producing O-alkyl oximes. The first procedure relates to a modification of the conventional method according to a two step process. In the first step of the procedure, an oxime is converted to the salt form by reaction with an alkali metal alkoxide. The oxime salt is isolated and dried. In the second step of the procedure, the alkali metal salt of the oxime is reacted with an alkyl bromide or alkyl chloride in an aprotic-dipolar solvent. Specifically, Linhart et al. discloses the conversion of the oxime to the corresponding sodium salt by reaction with sodium methoxide, isolating and drying the salt, and then reacting the salt with methyl chloride as the alkylating agent to produce the O-alkyl oxime.
The second procedure disclosed by Linhart et al. relates to the O-alkylation of oximes by reacting oximes with powdered sodium hydroxide and an organohalide in the presence of water by using an aprotic-dipolar solvent. The O-substituted oxime products are purified by fractional distillation.
H. S. Anker and H. T. Clarke, "Carboxymethoxylamine Hemihydrochloride", Org. Synth, Col. Vol. III, p. 173 discloses a process for the preparation of hydroxylamine O-acetic acid by reacting .alpha.-bromoacetic acid and acetoxime in the presence of sodium hydroxide in an aqueous reaction medium and hydrolyzing the resulting acetoxime O-acetic acid. Bromoacetic acid is used in excess in the process. However, Borek and Clarke, "Carboxymethoxylamine", J. Am. Chem. Soc., 58 2020 (1936) is cited therein for the use of chloroacetic acid in a reaction with acetoxime in which poorer yields (46-49%) of a product which was difficult to purify was recorded. The reaction requires heating in a tube at approximately 100.degree. C. The aqueous solution is saturated with solid sodium chloride prior to exhaustive extractions with ethyl ether to yield crude acetoxime O-acetic acid.
EPO Patent Application No. 158,159 to Mathew et al. relates to a process for producing O-substituted oxime compounds, specifically O-alkyl substituted oximes, by reacting an alkali metal or alkaline earth metal hydroxide compound with an excess of oxime reactant to form the oxime salt, removing water from the system by azeotropic distillation, and thereafter reacting the oxime salt with an organohalide compound under substantially anhydrous conditions. A key feature in this process is the azeotropic distillation of the oxime salt to remove all or a portion of the water from the reaction mixture prior to reacting the salt with an organohalide compound under substantially anhydrous conditions.
PCT/US89/02188 to Chempolil T. Mathew, relates to a process for producing O-substituted oximes under anhydrous conditions by reacting an alkali metal or alkaline earth metal hydroxide compound in an organic solvent with an excess of oxime reactant to form the oxime salt, removing water from the system by azeotropic distillation, and thereafter reacting at least about a two molar excess of the oxime salt in situ with an alpha-halocarboxylic acid and isolating the resultant O-substituted oxime compound from the reaction mixture. A key feature in this process is the azeotropic distillation of the oxime salt to remove all or a portion of the water from the reaction mixture prior to reacting at least about a two molar excess of the oxime salt in situ with an alpha-halocarboxylic acid. The O-substituted oxime compound can be isolated from the reaction mixture and purified employing conventional techniques.
Zhang, Feng and Shi, "The Preparation of Aminoxyacetic Acid", Chem. World, Vol. 9, No. 30, pp. 397-399, 1989 discloses condensing acetone oxime and chloroacetic acid in the presence of a solid acid or halide of a quaternary ammonium salt catalyst, organic solvent and sodium hydroxide at room temperature to form acetone oxime-acetic acid. Chloroacetic acid is added in excess relative to the acetone oxime. Benzene is used as the organic solvent. An approximately 6% aqueous solution of sodium hydroxide is used in an amount equimolar to the combined amount of acetone oxime and chloroacetic acid. After completion of the reaction, the aqueous solution is saturated with sodium chloride prior to exhaustive extractions with ethyl ether. Acetone oxime-acetic acid is obtained as a crude yellow oil which requires purification by vacuum distillation prior to hydrolysis to aminooxyacetic acid hemihydrochloride.
It is therefore an object of the present invention to provide an O-substituted oxime compound without the need for isolation or purification of an intermediate oxime salt compound.
Another object of the present invention is to provide a process for synthesizing an O-substituted oxime compound without removing, by azeotropic distillation or any means, all or a portion of the water added to the reaction mixture or formed during the production of an intermediate oxime salt compound.
A further object of the present invention is to provide a process for synthesizing an O-substituted oxime compound wherein the reaction of an intermediate oxime salt compound with an organohalide is not performed under substantially anhydrous conditions.
Another object of the present invention is to provide a process for synthesizing an O-substituted oxime compound having improved economics by avoiding the use of expensive alkoxides and by using organochlorides in place of bromides and iodides.
A further object of the present invention is to provide a process for synthesizing an O-substituted oxime compound which does not require an inert atmosphere.
Another object of the present invention is to provide an efficient process for synthesizing an O-substituted oxime compound in high yield and purity.
A further object of the present invention is to provide an efficient process for synthesizing aminooxyacetic acid in high yield and purity.
Another object of the present invention is to provide a process for synthesizing an O-substituted oxime compound wherein the O-substituted oxime compound can be extracted from the reaction medium at room temperature.
A further object of the present invention is to provide a process for synthesizing an O-substituted oxime compound without requiring the addition of a salt during the extraction of the O-substituted oxime compound.
Another object of the present invention is to provide a process for synthesizing an O-substituted oxime compound substantially free of a haloacetic acid.
A further object of the present invention is to provide a process for synthesizing an O-substituted oxime compound in the presence of an amount of water and under reaction conditions sufficient to remove substantially all of the haloacetic acid.